Prediction of intrinsic two-dimensional ferroelectrics in In2Se3 and other III2-VI3 van der Waals materials.

Interest in two-dimensional (2D) van der Waals materials has grown rapidly across multiple scientific and engineering disciplines in recent years. However, ferroelectricity, the presence of a spontaneous electric polarization, which is important in many practical applications, has rarely been reported in such materials so far. Here we employ first-principles calculations to discover a branch of the 2D materials family, based on In2Se3 and other III2-VI3 van der Waals materials, that exhibits room-temperature ferroelectricity with reversible spontaneous electric polarization in both out-of-plane and in-plane orientations. The device potential of these 2D ferroelectric materials is further demonstrated using the examples of van der Waals heterostructures of In2Se3/graphene, exhibiting a tunable Schottky barrier, and In2Se3/WSe2, showing a significant band gap reduction in the combined system. These findings promise to substantially broaden the tunability of van der Waals heterostructures for a wide range of applications.

Substrate Facet Effect on the Growth of Monolayer MoS2 on Au Foils.

MoS2 on polycrystalline metal substrates emerges as an intriguing growth system compared to that on insulating substrates due to its direct application as an electrocatalyst in hydrogen evolution. However, the growth is still indistinct with regard to the effects of the inevitably evolved facets. Herein, we demonstrate for the first time that the crystallography of Au foil substrates can mediate a strong effect on the growth of monolayer MoS2, where large-domain single-crystal MoS2 triangles are more preferentially evolved on Au(100) and Au(110) facets than on Au(111) at relative high growth temperatures (>680 °C). Intriguingly, this substrate effect can be weakened at a low growth temperature (∼530 °C), reflected with uniform distributions of domain size and nucleation density among the different facets. The preferential nucleation and growth on some specific Au facets are explained from the facet-dependent binding energy of MoS2 according to density functional theory calculations. In brief, this work should shed light on the effect of substrate crystallography on the synthesis of monolayer MoS2, thus paving the way for achieving batch-produced, large-domain or domain size-tunable growth through an appropriate selection of the growth substrate.

Signaling of glial cell line-derived neurotrophic factor and its receptor GFRα1 induce Nurr1 and Pitx3 to promote survival of grafted midbrain-derived neural stem cells in a rat model of Parkinson disease.

Glial cell line-derived neurotrophic factor (GDNF) and its receptor GFRα1 have been implicated in the survival of ventral midbrain dopaminergic (DA) neurons, but the molecular mechanisms bywhich GDNF generates DA neurons in grafted midbrain-derived neural stem cells (mNSCs) are not understood. Midbrain-derived neural stem cells isolated from rat embryonic mesencephalon (embryonic day 12) were treated with GDNF or in combination with GFRα1 small interfering RNA. Reverse transcription-polymerase chain reaction, Western blot, and immunocytochemistry were used totest the expression of the orphan nuclear receptor Nurr1 and thetranscription factor Pitx3 and newborn tyrosine hydroxylase (TH)-positive cells. Treatment of mNSCs with GDNF increased mNSCs' sphere diameter, reduced expression of caspase 3, and increased expression of Bcl-2. Glial cell line-derived neurotrophic factor-treated mNSCs enhanced Nurr1 and Pitx3 expression and the fraction of TH-, TH/Pitx3-, and TH/Nurr1-positive cells in culture. Grafted GDNF-treated mNSCs significantly decreased apomorphine-induced rotation behavior in 6-hydroxydopamine-lesioned rats. Glialcell line-derived neurotrophic factor-treated mNSCs showed increased numbers of TH/Pitx3- and TH/Nurr1-postivie cells. The effect elicited by GDNF was inhibited by small interfering RNA-mediated knockdown of GFRα1. Our data demonstrate the contribution of GDNF to DA neuron development and may also elucidate pathogenetic mechanisms in Parkinson disease and contribute to the development of novel therapies for the disorder.

[Parthenolide inhibits neuroinflammation and promotes neurogenesis in the ischemic striatum following transient middle cerebral artery occlusion in the adult rat brain].

AIM: The objective of this study was to test the hypothesis that parthenolide suppresses ischemia-induced neuroinflammation in the MCAO model of adult rat. METHODS: MCAO rats were treated i.p. with parthenolide (500 microg/kg). Brain sections were analyzed for BrdU, BrdU-DCX, BrdU-Tuj-1, BrdU-MAP-2 and BrdU-GFAP staining. Total protein was extracted from ischemic striatum, and Western blot was used to determine TNF-alpha expression. RESULTS: Cerebral ischemia increases expression of TNF-alpha in the ischemic striatum. Parthenolide suppressed the expression of TNF-alpha and enhances the proliferation of newborn cells in the ischemic striatum. The cell number of BrdU(+)-DCX(+), BrdU(+)-Tuj-1(+), and BrdU(+)-MAP-2(+) is increased in the ischemic striatum after parthenolide treatment at 3 d, 7 d or 28 d after MCAO. Furthermore, parthenolide depressed the cell number of BrdU(+)-GFAP(+) in the ischemic striatum at 3 d, 7 d and 28 d after MCAO. CONCLUSION: Parthenolide inhibits neuroinflammation induced by cerebral ischemia and promotes neurogenesis in the ischemic striatum. Further study of the effects of parthenolide on inflammatory gene expression using model animal systems as described here are critical to elucidating their mechanisms of action.

Quantitative determination of the anticancer agent tubeimoside I in rat plasma by liquid chromatography coupled with mass spectrometry.

Tubeimoside I is an important component isolated from Bolbostemma paniculatum. Tubeimoside I has been demonstrated to possess many pharmacological activities, including anti-inflammatory, antitumor, and antitumor-promoting effects. The purpose of the present study was to examine in vivo pharmacokinetics and bioavailability of tubeimoside I in rats by using a liquid chromatography coupled with mass spectrometry quantitative detection method (LC/MS). The plasma samples were deproteinated, evaporated and reconstituted in 100 microl methanol prior to analysis. The separation was performed by Waters Symmetry C18 reversed-phase column (3.5 microm, 150 mm x 2.1mm, Waters Inc., USA) and a SB-C18 guard column (5 microm, 20 mm x 4.0mm). The mobile phase was a mixture of acetonitrile and water containing 5 microM NaAc (60:40, v/v). The method was validated within the concentration range 20-5000 ng/ml, and the calibration curves were linear with correlation coefficients >0.999. The lowest limit of quantitation (LLOQ) for tubeimoside I was 20 ng/ml in 0.1 ml rat plasma. The intra-assay accuracy and precision ranged from 92.4 to 104.9% and from 5.8 to 10.5%, respectively, while inter-assay accuracy and precision ranged from 94.2 to 95.0% and from 5.1 to 8.8%, respectively. The method was further applied to assess pharmacokinetics and oral bioavailability of tubeimoside I after intravenous and oral administration to rats. The oral bioavailability of tubeimoside I is only 0.23%, which indicates that tubeimoside I has poor absorption or undergoes acid-induced degradation. Practical utility of this new LC/MS method was confirmed in pilot pharmacokinetic studies in rats following both intravenous and oral administration.

Bioavailabilty and pharmacokinetics of four active alkaloids of traditional Chinese medicine Yanhuanglian in rats following intravenous and oral administration.

Corydalis saxicola Bunting (Yanhuanglian) is an important component in various prescriptions in traditional Chinese medicine. Yanhuanglian has been demonstrated to possess many pharmacological activities, including antibacterial, antiviral and anticancer activities. The active fractions are dehydrocavidine, coptisine, dehydroapocavidine and tetradehydroscoulerine. The purpose of the present study was to examine in vivo pharmacokinetics and tissue distribution in rats by using high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometry. Systemic clearance of the four active alkaloids in plasma was over 93% of hepatic blood flow, indicating they may be quickly eliminated via hepatic clearance. Less than 10% drugs was excreted via urine following intravenous and oral administration, suggesting that these four alkaloids may undergo significant metabolism in the body or the drug may be excreted via other routes other than urine. There was significantly lower excretion of these four alkaloids following oral than intravenous administration, suggesting a significant first pass effect after oral administration. There appeared to be wide distribution of those four alkaloids in rats as demonstrated by the higher apparent volume of distribution. Our results have also demonstrated that the four alkaloids can be absorbed following oral administration although there were less than 15% of drugs absorbed into systemic circulation. In summary, the favorable oral bioavailability properties of those four active alkaloids in rats make Yanhuanglian extract worth further investigation for improving oral bioavailability.

[Experimental research on immunological rejection in neural stem cells allograft].

AIM: To investigate the occurrence of immunological rejection in brain transplantation of neural stem cells (NSCs) in the rat of Parkinson's disease model. METHODS: NSCs derived from the brain of E14.5d SD rat were cultured in vitro. Single cell suspensions were grafted into the striatum of the rat model of Parkinson's disease. Surviving animals were sacrificed at 10, 21, 35 and 60 d after transplantation, and the brain tissue was stained with HE and immunocytochemically to detect the expression of tyrosine hydroxylase (TH), CD4, CD8 and major histocompatibility complex class II antigens (MHC-II). RESULTS: The expression of elicited CD4, CD8 and MHC-II was detected within and around the allografts in the graft groups at 10 and 21 d after grafting and was subsiding at 35 d. At 60 d only very occasional immunopositive cells were present. The number of TH positive neurons was low at 10, 21 d, but increased at 35 d and 60 d. There was no significant difference between negative and positive control groups at different time points. The rotation behavior of PD was decreased 35 d after transplantation. CONCLUSION: Intracerebral transplantation of NSCs did not cause remarkable immunological rejection.

Simultaneous determination of four active alkaloids from a traditional Chinese medicine Corydalis saxicola Bunting. (Yanhuanglian) in plasma and urine samples by LC-MS-MS.

A sensitive rapid method for the simultaneous determination of four major active alkaloids (dehydrocavidine, coptisine, dehydroapocavidine, and tetradehydroscoulerine, in abbreviation thereafter called YHL-I, YHL-II, YHL-III, and YHL-IV, respectively) from a Chinese traditional medicine Corydalis saxicola Bunting. (Yanhuanglian) in rat plasma and urine was established and validated. The assay for these substances in plasma and urine was based on HPLC coupled with tandem mass spectrometry (MS/MS) detection using multiple reaction monitoring mode (MRM) with berberine and clenbuterol as internal standards. The plasma and urine sample were deproteinated by adding methanol prior to liquid chromatography where separation was performed on a Luna column (5 microm, 100 x 2.00 mm) and an Agilent Zorbax SB-C18 guard column (5 microm, 20 x 4 mm). The method was validated with the concentration range 1-1000 ng/mL in plasma and 10-1000 ng/mL in urine for the four test compounds, and the calibration curves were linear with correlation coefficients >0.999. The lowest limits of quantitation for all four substances were 1 ng/mL in 0.1 mL rat plasma and 10 ng/mL in 0.1 mL urine. The intra-assay accuracy and precision in plasma ranged from 88.1 to 115.7% and 1.4 to 10.8%, respectively, while inter-assay accuracy and precision for YHL-I, YHL-II, YHL-III, and YHL-IV ranged from 96.2 to 113.2% and 0.4 to 16.9%, respectively. The intra-assay accuracy and precision for YHL-I, YHL-II, YHL-III, and YHL-IV in rat urine ranged from 96.1 to 112.9% and 1.2 to 8.3%, respectively, while inter-assay accuracy and precision ranged from 95.0 to 106.8% and 2.2 to 10.3%, respectively. The method was further applied to assess pharmacokinetics and urine excretion of the four alkaloids after oral and intravenous administration to rats. Practical utility of this new LC-MS-MS method was confirmed in pilot pharmacokinetic studies in rats following both intravenous and oral administration.